Flashcards in Lecture 8 Amino Acids Deck (58):
Amino acid synth, amino degradation, derivatives of AA, urea cycle.
Energy used for
Heat, mechanical movement, electrical work, chemical energy can be stored or used as food.
Release of energy, water, CO2.
Glucose to glycogen, Glycerol+fatty acids to triglycerides, amino acids to proteins. Most of this happens in the liver
Glycogen to glucose, triglycerides to glycerol + fatty acids, proteins to AAs (obtain essential AAs this way). Most of this happens in the liver
Carbs - glucose (+other monosaccharides)
Fats - triglycerides (glycerol, fatty acids)
Proteins - aas
Using aas as energy
First you have to get rid of nitrogen. AAs feed into becoming pyruvate (3 carbon - used for glucose production), acetyl CoA (2 carbon, not for glucose). TCA cycle and ETC can be used later from these.
Breaking down nutrients
AAs and glycerol can be converted to pyruvate (glucose later). Needed for CNS and RBCs. Lean tissue goes when body runs out of glucose. Adequate carbs prevent this. Fatty acids are converted to Acetyl-CoA (not for glucose).
Quick energy - convert to lactate (anaerobic). Sustained for just a few minutes.
SLower energy - convert to acetyl CoA - aerobic.
Lactic acid travels to the liver
–the liver converts it back to glucose --This is called the Cori cycle
Pyruvate to Acetyl CoA
If o2 is available. Pyruvate enters mitochondria, –produce 2 acetyl CoA.
Convert to pyruvate
COnvert to acetyl CoA
they can be used for energy or converted to fatty acids and stored as triglyceride.
–Some enter the TCA cycle directly
Dietary protein is the main source of amino acid. In the process of digestion, proteins are broken down to free aa in the gastrointestinal tract. The resulting alpha-keto acid is then used as fuel, or as a biosynthetic intermediate.
Unlike carbohydrates and lipids, aa do not have a dedicated storage form equivalent to glycogen or fat.
When aa are metabolized, the resulting excess nitrogen must be excreted.
Remove amine group from AAs in liver.
Stomach - HCl breaks down, denatures, small peptides. Intestines - other proteases get it to AAs and some dipeptides. Transport across small intestine lining.
AAs to body proteins, Glucose to glycogen
Removal of amino group, use of nitrogen in synth of new nitrogen compounds, passage of nitrogen into urea cycle, incorporation of carbon atoms into compounds for CAC cycle.
Our body does not store
Nitrogen containing compounds.
Use alpha ketoglutarate as amino group nitrogen acceptor. This is converted to glutamate.
Exchange amino group with carbonyl. No net loss of N2.
Alanine can be converted to
pyruvate and glutamate from alanine and oxoglutarate (all 3 carbon atoms, all of these conversion reactions are bidirectional).
All amino groups go through glutamate. Transaminase reactions are easily reversible. Concentrations determine where it goes.
Equilibriate amino groups among available alpha keto acids.
Although the amino N of one amino acid can be used to synthesize another amino acid, N must be obtained in the diet as amino acids (proteins).
Proceed through urea cycle before excretion (processing occurs in liver).
Ammonia is highly toxic to living organisms and must be eliminated safely. Fish excrete ammonia through their gills directly into the surrounding water and mammals converts ammonia to non-toxic urea via the urea cycle.
The conversion of ammonia to urea takes place in the liver. From there urea is transported to the kidneys and transferred to urine for excretion.
Removal of a molecule of water by a dehydratase
he oxidative removal of the amino group, resulting in keto acids and ammonia
Removal of a molecule of water by a dehydratase
serine or threonine dyhydratase; this reaction produces an unstable, imine intermediate that hydrolyzes spontaneously to yield an α-keto acid and ammonia
Catalyzes rxn that removes N from the amino acid pool. Takes N from glutamate to form alpha-ketoglutarate (now this can go back to grab a different ammonia).
Pyridoxal phosphate dependent
Product is pyruvate
Remove H20, leaving unstable intermediate. This will spontaneously remove ammonia and form pyruvate.
BUN (blood urea nitrogen). Monitored in patients with amino acid metabolism disorders or renal problems. Measure the action of urease by monitoring ammonia product with a color reagent.
Monosodium Glutamate - MSG
Food additive. Can cause weakness, tingling and a sensation of warmth in the face and upper torso. Symptoms generally last about 30 minutes. No permanent damage, but could trigger bronchospasms (asthma).
Also a neurotransmitter - can be decarboxylated to form GABA, another neurotransmitter.
Alanine as a carrier
Transported from peripheral tissues to liver, converted to pyruvate with nitrogen incorporated into urea
Pyrovate can be used to produce glucose (gluconeogenesis)
This glucose-alanine cycle allows the net conversion of amino acid carbons to glucose
Carbons are returned to peripheral tissues as glucose
Alanine and glutamine are released in similar amounts from muscle
Account for about 50% or amino acids released by muscle into the blood
Alanine and Glutamine flow
The amount of alanine and glutamine released far exceeds the proportion of these Aas in muscle proteins
Large amounts of remodeling of protein-derived amno acids occurs by transaminations
Need to ingest excess
Birds and reptiles
Birds and reptiles
First metabolic cycle detected. Krebs & Henseleit. Urea H2N-(CO)-NH2, 2 nitrogens
1 from ammonia through carbamoyl phosphate
NH3 + HCO3- + 2ATP
1 from Aspartic acid
α-ketoglutarate + NH4+ + NADH + H+
Carbon from bicarbonate (unfixed)
Urea cycle also excretes bicarbonate breakdown product of carboxylic acids
**Starts in mito**
Inherited disorders of urea cycle
Loss of cycle catastrophic
Ammonia toxic to brain coma
See with liver failure
Do not see genetic diseases with total loss
Genetic partial deficiencies retardation
Treatment with low protein diets
Supplement with keto-acids
Mops up excess NH3
If choose wisely, can get essential amino acids made (e.g., α-ketoisovalerate valine)
Treatment of genetic deficiencies in urea cycle enzymes
Aromatic groups can help
First step required
transamination→ glutamate or aspartate
Increase glucose - certain AAs are both glucogenic and ketogenic.
Increase ketone bodies.
Maple syrup urine disease
Inherited. Loss of the α-amino group, followed by oxidative decarboxylation of the resulting α-keto acid to produce a CoA derivative
Decarboxylation catalyzed by branched-chain keto acid decarboxylase (IM of mitochondria)
Untreated lead to both physical and mental retardation
Defect can be managed with a low-protein diet or modified diet or supplementation with high doses of thiamine pyrophosphate
Deficiency of phenylalanine hydroxylase. Untreated leads to excretion of phenylpyruvate and phenyllactate. Can result in severe retardation. Individuals, very light skin, unusual gait, stance
Alkaptonuria (black urine disease)
Deficiency in phenylalanine-tyrosine pathway, the enzyme that catabolizes the oxidation of homogentisic acid
Homogentisic acid accumulates and is excreted in the in urine (1 in 1,000,000 births). This compound gives urine a dark color
Individual: dark pigment in cartilage tissue, with subsequent tissue damage, and severe arthritis
Only symptomatic relief
Lack of pigmentation (amino acid pathways). Blue eyes, light blond hair. Lack enzyme tyrosinase.
2-step hydroxylation of tyrosine to dihydroxyphenylalanie (DOPA) and further oxidation to a quinone, a precursor of melanin
derived from tryptophan and serotonin.